A death-associated protein kinase (DAPK)-interacting protein, DIP-1, is an E3 ubiquitin ligase that promotes tumor necrosis factor-induced apoptosis and regulates the cellular levels of DAPK
A death-associated protein kinase (DAPK)-interacting protein, DIP-1, is an E3 ubiquitin ligase that promotes tumor necrosis factor-induced apoptosis and regulates the cellular levels of DAPK
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DOI：
10.1074/jbc.m208585200
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发表时间：
2002-12-06
影响因子：
4.8
通讯作者：
Gallagher, PJ
中科院分区：
文献类型：
--
作者：
Jin, YJ;Blue, EK;Gallagher, PJ
死亡相关蛋白激酶（Death-associated protein kinase，DAPK）是一种多结构域的丝氨酸/苏氨酸蛋白激酶，在细胞凋亡调控中起重要作用。在这些研究中，我们已经确定了一种称为DIP-1的DAPK相互作用蛋白，这是一种新型的多环指蛋白。DIP-1的RING指基序具有E3连接酶活性，可以在体外自动泛素化DIP-1。在体内，DIP-1被检测为多泛素化蛋白，表明DIP-1的细胞内水平受泛素-蛋白酶体系统调节。DIP-1在HeLa细胞中的瞬时表达拮抗DAPK的抗凋亡功能以促进半胱天冬酶依赖性凋亡。这些研究还表明，DAPK是DIP-1泛素化的体外和体内靶点，从而提供了一种通过蛋白酶体降解调节DAPK活性的机制。
Death-associated protein kinase (DAPK) is a multidomain Ser/Thr protein kinase with an important role in apoptosis regulation. In these studies we have identified a DAPK-interacting protein called DIP-1, which is a novel multi-RING finger protein. The RING finger motifs of DIP-1 have E3 ligase activity that can auto-ubiquitinate DIP-1 in vitro. In vivo, DIP-1 is detected as a polyubiquitinated protein, suggesting that the intracellular levels of DIP-1 are regulated by the ubiquitin-proteasome system. Transient expression of DIP-1 in HeLa cells antagonizes the anti-apoptotic function of DAPK to promote a caspase-dependent apoptosis. These studies also demonstrate that DAPK is an in vitro and in vivo target for ubiquitination by DIP-1, thereby providing a mechanism by which DAPK activities can be regulated through proteasomal degradation.